More attention should be paid to Omicron-associated sepsis: a multicenter retrospective study in south China.

Background: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible but causes less severe disease compared to other variants. However, its association with sepsis incidence and outcomes is unclear. This study aimed to investigate the incidence of Omicron-associated sepsis, as per the Sepsis 3.0 definition, in hospitalized patients, and to explore its relationship with clinical characteristics and prognosis. Methods: This multicenter retrospective study included adults hospitalized with confirmed SARS-CoV-2 infection across six tertiary hospitals in Guangzhou, China from November 2022 to January 2023. The Sequential Organ Failure Assessment (SOFA) score and its components were calculated at hospital admission to identify sepsis. Outcomes assessed were need for intensive care unit (ICU) transfer and mortality. Receiver operating characteristic curves evaluated the predictive value of sepsis versus other biomarkers for outcomes. Results: A total of 299 patients (mean age: 70.1±14.4 years, 42.14% female) with SOFA score were enrolled. Among them, 152 were categorized as non-serious cases while the others were assigned as the serious group. The proportion of male patients, unvaccinated patients, patients with comorbidity such as diabetes, chronic cardiovascular disease, and chronic lung disease was significantly higher in the serious than non-serious group. The median SOFA score of all enrolled patients was 1 (interquartile range, 0-18). In our study, 147 patients (64.19%) were identified as having sepsis upon hospital admission, with the majority of these septic patients (113, representing 76.87%) being in the serious group, the respiratory, coagulation, cardiovascular, central nervous, and renal organ SOFA scores were all significantly higher in the serious compared to the non-serious group. Among septic patients, 20 out of 49 (40.81%) had septic shock as indicated by lactate measurement within 24 hours of admission, and the majority of septic patients were in the serious group (17/20, 76.87%). Sepsis was present in 118 out of 269 (43.9%) patients in the general ward, and among those with sepsis, 34 out of 118 (28.8%) later required ICU care during hospitalization. By contrast, none of the patients without sepsis required ICU care. Moreover, the mortality rate was significantly higher in patients with than without sepsis. Conclusions: A considerable proportion of patients infected with Omicron present with sepsis upon hospital admission, which is associated with a poorer prognosis. Therefore, early recognition of viral sepsis by evaluation of the SOFA score in hospitalized coronavirus disease 2019 patients is crucial.

Prognostic and risk factor analysis of cancer patients after unplanned ICU admission: a real-world multicenter study.

To investigate the occurrence and 90-day mortality of cancer patients following unplanned admission to the intensive care unit (ICU), as well as to develop a risk prediction model for their 90-day prognosis. We prospectively analyzed data from cancer patients who were admitted to the ICU without prior planning within the past 7 days, specifically between May 12, 2021, and July 12, 2021. The patients were grouped based on their 90-day survival status, and the aim was to identify the risk factors influencing their survival status. A total of 1488 cases were included in the study, with an average age of 63.2 ± 12.4 years. The most common reason for ICU admission was sepsis (n = 940, 63.2%). During their ICU stay, 29.7% of patients required vasoactive drug support (n = 442), 39.8% needed invasive mechanical ventilation support (n = 592), and 82 patients (5.5%) received renal replacement therapy. We conducted a multivariate COX proportional hazards model analysis, which revealed that BMI and a history of hypertension were protective factors. On the other hand, antitumor treatment within the 3 months prior to admission, transfer from the emergency department, general ward, or external hospital, high APACHE score, diagnosis of shock and respiratory failure, receiving invasive ventilation, and experiencing acute kidney injury (AKI) were identified as risk factors for poor prognosis within 90 days after ICU admission. The average length of stay in the ICU was 4 days, while the hospital stay duration was 18 days. A total of 415 patients died within 90 days after ICU admission, resulting in a mortality rate of 27.9%. We selected 8 indicators to construct the predictive model, which demonstrated good discrimination and calibration. The prognosis of cancer patients who are unplanned transferred to the ICU is generally poor. Assessing the risk factors and developing a risk prediction model for these patients can play a significant role in evaluating their prognosis.

Effects of carrimycin on biomarkers of inflammation and immune function in tumor patients with sepsis: A multicenter double-blind randomized controlled trial.

Carrimycin is a potential immune-regulating agent for sepsis in patients with tumors. In this study, we investigated its effects on inflammation and immune function in tumor patients with sepsis. In total, 120 participants were randomized to receive either carrimycin treatment (400 mg/day) (n = 62) or placebo (n = 58) for 7 days. The primary outcomes were immune-related indicators. Subsequently, patients were stratified into two subgroups (CD4 < 38.25% and CD8 < 25.195%). Ninety-nine participants were analyzed: 47 and 52 in the carrimycin and placebo groups, respectively. HLA-DR levels were rapidly increased in the carrimycin group; however, the placebo group initially experienced a decline in HLA-DR level at 1 day after administration. In the subgroup with CD4 < 38.25%, the carrimycin group exhibited significantly higher HLA-DR levels than the placebo group (2.270, P = 0.023) 1 day after administration and the degree of increase in HLA-DR in the carrimycin group was higher than that in the placebo group (2.057, P = 0.040). In the CD8 < 25.195% subgroup, the carrimycin group demonstrated significantly higher levels of CD8+ T cells than the placebo group at 3 (2.300,P = 0.027) and 5 (2.106, P = 0.035) days after administration. Carrimycin intervention led to significant reductions in the SOFA, APACHE II, PCT, and CRP levels. No adverse events were observed. In tumor patients with sepsis, particularly in those experiencing immunological suppression, carrimycin effectively regulates immune responses by increasing HLA-DR and CD8+ T cell levels and plays an anti-infective role, reducing disease severity. (Chictr.org.cn, ID Number: ChiCTR2000032339).

GABRP is a Promising Prognostic Biomarker and Associated with Immune Cell Infiltration in Lung Squamous Cell Carcinoma.

Background: GABRP has been reported to play an oncogenic role in various carcinomas. However, no report has been found for its involvement in lung squamous cell carcinoma (LUSC) development yet. We aimed to explore the expression and prognostic roles of GABRP and assessment of its association with tumor microenvironment in LUSC. Methods: The GABRP expression in LUSC was analyzed using TCGA, GEO, and HPA databases. The Kaplan-Meier, Cox regression analysis, and receiver operating characteristic (ROC) curve were applied to assess the prognostic and diagnostic values of GABRP in LUSC. We also performed ESTIMATE and ssGSEA to explore the association between GABRP expression and immune cell infiltrations. GABRP was highly expressed in LUSC patients, and up-regulation of GABRP was associated with shorter overall survival (OS). Cox regression analysis indicated that GABRP was an independent prognostic factor for LUSC patients. KEGG analysis revealed that GABRP may play an important role in starch and sucrose metabolism and nicotine addiction. Specifically, GABRP expression showed significant positive correlations with the infiltration levels of most types of immune cells, as well as immune checkpoint molecules expression. Conclusion: Up-regulation of GABRP in LUSC could be severed as a prognostic marker and a potential target for immunotherapy in LUSC.

LncRNA SNHG15 regulates hypoxic-ischemic brain injury via miR-153-3p/SETD7 axis.

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of fatality and morbidity in newborns. Long non-coding RNAs (lncRNAs) Small Nucleolar RNA Host Gene 15 (SNHG15) was elevated in the peripheral blood of patients with acute cerebral ischemia, but its role in HI brain injury remained elusive. Hence, this study aimed to investigate the effect of SNHG15 on HI brain injury and study the precise mechanism of action. In this study, a mouse model of HI brain injury was established through ligating right carotid arteries. The oxygen-glucose deprivation (OGD) model was established in PC12 cells. Results showed that SNHG15 was elevated in brain tissues of mice with HI brain injury, and knockdown of SNHG15 attenuated HI-induced impairment of neurobehavioral function, brain edema, brain injury, and cell apoptosis. Besides, SNHG15 acted as a miR-153-3p sponge. SETD7 was identified to be a target of miR-153-3p. Furthermore, down-regulation of SNHG15 inhibited the OGD-induced increase in SETD7 expression in PC12 cells. Moreover, SNHG15 modulated OGD-induced cell apoptosis and decrease of cell viability through the miR-153-3p/SETD7 axis. In conclusion, knockdown of SNHG15 alleviated HI brain injury through modulating the miR-153-3p/ SETD7 axis. SNHG15 may be a prospective target for HIE therapy.

Atractylenolide III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

PURPOSE: To evaluate the influence of atractylenolide (Atr) III on sepsis-induced lung damage. METHODS: We constructed a mouse sepsis model through cecal ligation and puncture. These mice were allocated to the normal, sepsis, sepsis + Atr III-L (2 mg/kg), as well as Atr III-H (8 mg/kg) group. Lung injury and pulmonary fibrosis were accessed via hematoxylin-eosin (HE) and Masson's staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry for detecting sepsis-induced lung cell apoptosis. The contents of the inflammatory cytokines in lung tissue were measured via enzyme-linked immunosorbent assay (ELISA). RESULTS: Atr III-H did not only reduce sepsis-induced lung injury and apoptosis level, but also curbed the secretion of inflammatory factors. Atr III-H substantially ameliorated lung function and raised Bcl-2 expression. Atr III-H eased the pulmonary fibrosis damage and Bax, caspase-3, Vanin-1 (VNN1), as well as Forkhead Box Protein O1 (FoxO1) expression. CONCLUSIONS: Atr III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

Atractylenolide III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein

ABSTRACT Purpose: To evaluate the influence of atractylenolide (Atr) III on sepsis-induced lung damage. Methods: We constructed a mouse sepsis model through cecal ligation and puncture. These mice were allocated to the normal, sepsis, sepsis + Atr III-L (2 mg/kg), as well as Atr III-H (8 mg/kg) group. Lung injury and pulmonary fibrosis were accessed via hematoxylin-eosin (HE) and Masson's staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry for detecting sepsis-induced lung cell apoptosis. The contents of the inflammatory cytokines in lung tissue were measured via enzyme-linked immunosorbent assay (ELISA). Results: Atr III-H did not only reduce sepsis-induced lung injury and apoptosis level, but also curbed the secretion of inflammatory factors. Atr III-H substantially ameliorated lung function and raised Bcl-2 expression. Atr III-H eased the pulmonary fibrosis damage and Bax, caspase-3, Vanin-1 (VNN1), as well as Forkhead Box Protein O1 (FoxO1) expression. Conclusions: Atr III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

Metoclopramide or domperidone improves post-pyloric placement of spiral nasojejunal tubes in critically ill patients: a prospective, multicenter, open-label, randomized, controlled clinical trial.

INTRODUCTION: The use of prokinetic agents on post-pyloric placement of spiral nasojejunal tubes is controversial. The aim of the present study was to examine if metoclopramide or domperidone can increase the success rate of post-pyloric placement of spiral nasojejunal tubes. METHODS: A multicenter, open-label, randomized, controlled trial was conducted in seven hospitals in China between April 2012 and February 2014. Patients admitted to the intensive care unit and requiring enteral nutrition for more than three days were randomly assigned to the metoclopramide, domperidone or control groups (1:1:1 ratio). The primary outcome was defined as the success rate of post-pyloric placement of spiral nasojejunal tubes, assessed 24 hours after initial placement. Secondary outcomes included success rate of post-D1, post-D2, post-D3 and proximal jejunum placement and tube migration distance. Safety of the study drugs and the tubes during the entire study period were recorded. RESULTS: In total, 307 patients were allocated to the metoclopramide (n = 103), domperidone (n = 100) or control group (n = 104). The success rate of post-pyloric placement after 24 hours in the metoclopramide, domperidone and control groups was 55.0%, 51.5% and 27.3%, respectively (P = 0.0001). Logistic regression analysis identified the use of prokinetic agents, Acute Physiology and Chronic Health Evaluation (APACHE) II score <20, Sequential Organ Failure Assessment (SOFA) score <12 and without vasopressor as independent factors influencing the success rate of post-pyloric placement. No serious drug-related adverse reaction was observed. CONCLUSIONS: Prokinetic agents, such as metoclopramide or domperidone, are effective at improving the success rate of post-pyloric placement of spiral nasojejunal tubes in critically ill patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-12001956 . Registered 21 February 2012.

Low concentration of metformin induces a p53-dependent senescence in hepatoma cells via activation of the AMPK pathway.

The induction of senescence for cancer treatment has provoked considerable interest recently. Metformin, a first-line drug for diabetes mellitus type 2, appears to be associated with a lower risk and improved outcomes in hepatocellular carcinoma (HCC). The mechanism involved in function of metformin in HCC is poorly understood. We show that low doses of metformin induced hepatoma cell senescence characterized by accumulation of senescence-associated ß-galactosidase activity (SA-ß-gal) and the senescence marker Dec1, whereas the higher doses initiated apoptotic cell death. Metformin-induced senescence was accompanied by enhanced phosphorylation levels of AMP-activated protein kinase (AMPK) and its downstream target acetyl-CoA carboxylase (ACC). The expression of acetylated p53 at Lys382 (Ac-p53) and p21 was also increased, while phosphorylation of p53 at Ser15 (p-p53), p53, p16 and pRB was rarely altered after metformin treatment. Moreover, inhibition of AMPK decreased p-AMPK, p-ACC, Ac-p53 and p21 expression, diminished SA-ß-gal staining and restored hepatoma cell proliferation. In addition, p53 siRNA transfection attenuated metformin-induced SA-ß-gal staining. Intriguingly, co-expression of SIRT1 and p53 dramatically reduced the levels of Ac-p53, however, low doses of metformin treatment partially reversed the effect of SIRT1 on p53 acetylation and elevated SA-ß-gal activity. These observations indicate that activation of the AMPK pathway promotes senescence in hepatoma cells exposed to low concentrations of metformin in a p53-dependent manner. Further, low doses of metformin may have the potential to be used as an adjuvant to HCC therapy.

Effect of automatic versus fixed continuous positive airway pressure for the treatment of obstructive sleep apnea: an up-to-date meta-analysis.

PURPOSE: This study was made to evaluate the effect of automatic continuous positive airway pressure (auto-CPAP) versus fixed continuous positive airway pressure (fixed CPAP) in reducing the apnea-hypopnea index (AHI) and the mean therapy pressure, improving subjective sleepiness, sleep architecture, patient compliance, and preference in patients with obstructive sleep apnea. METHODS: We searched the electronic databases MEDLINE, EMBASE, the Cochrane Library, and Google Scholar. Randomized controlled trials comparing auto-CPAP with fixed CPAP were reviewed. Continuous variables were presented as mean difference (MD), and dichotomous data as odds ratio (OR), both with 95% confidence intervals (CI). RESULTS: We identified 19 studies consisting of 845 patients. Compared to fixed CPAP, the use of auto-CPAP reduced mean therapy pressure (MD -1.64; 95% CI -2.46 to -0.82), improved patient compliance (MD 0.23; 95% CI 0.06 to 0.39), increased the percentage of total sleep time (TST) in slow wave sleep (MD 5.11; 95% CI 1.34 to 8.88), and decreased the percentage of TST in stage 2 sleep (MD -4.75; 95% CI -9.38 to -0.11). Moreover, more patients preferred auto-CPAP therapy (OR 3.65; 95% CI 1.27 to 10.53). There were nonsignificant trends towards better outcomes with auto-CPAP for AHI and Epworth Sleepiness Scale (MD -0.43; 95% CI -1.10 to 0.23, and MD -0.24; 95% CI -0.74 to 0.25, respectively), though these are of questionable clinical significance. CONCLUSIONS: There are some aspects of clinical care, such as a mild improvement in compliance, patient preference, and sleep architecture that appear to favor the use of auto-CPAP compared to fixed CPAP. The clinical relevance of these findings requires further study.

[Role of inflammation factors in impaired glucose tolerance and sleep apnea/hypopnea syndrome in pregnant women].

OBJECTIVE: To investigate the possible role of inflammation factors in the pathogenesis of impaired glucose tolerance (IGT) with concurrent obstructive sleep apnea/hypopnea syndrome (OSAHS) in pregnant women. METHODS: Twenty-five pregnant women with IGT and concurrent OSAHS and 35 pregnant women with IGT but not OSAHS were monitored for all night polysomnography (PSG), and the apnea hypopnea index (AHI) and the lowest pulse oxygen saturation (LSpO2) were recorded. The body mass index, glycated serum protein (GSP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured in these women. RESULTS: IL-6 and TNF-α levels increased significantly in women with IGT and OSAHS as compared with those in women without OSAHS. AHI showed significant positive correlations to GSP, IL-6 and TNF-α, whereas LSpO2 was inversely correlated to GSP, IL-6 and TNF-α. IL-6 and TNF-α were significantly correlated to GSP, with correlation coefficients of 0.510 and 0.476, respectively. CONCLUSION: The inflammatory factors may play important roles in IGT complicated by OSAHS in pregnant women, and as a potential risk factor, OSAHS may contribute to the occurrence of progression of IGT.

[Relation of advanced oxidation protein products with VEGF and TGF-ß1 in colon cancer cells exposed to intermittent hypoxia].

OBJECTIVE: To investigate the association of advanced oxidation protein products (AOPP) with oxidative stress in colon cancer cells exposed to intermittent hypoxia (IH). METHODS: Colon cancer SW480 cells were exposed to IH, continuous hypoxia, or normoxia. Enzyme-linked immunosorbent assay (ELISA) was employed to examine the levels of AOPP and vascular endothelial growth factor (VEGF), xanthine oxidase assay was used to determine malonaldehyde (MDA) and glutathione peroxidase (GSH-PX), and Western blotting and immunofluorescence assay were performed for detection of transforming growth factor-ß(1) (TGF-ß(1)) expression. RESULTS: Compared with the normoxia group, the two hypoxia groups showed significantly increased AOPP and MDA levels (P<0.05) and lowered SOD and GSH-PX levels (P<0.05). The concentration of AOPP was positively correlated to MDA, VEGF, and TGF-ß(1) levels (P<0.05), but inversely to SOD. No significant correlation was found between AOPP and GSH-PX levels. CONCLUSION: Compared with continuous hypoxia, IH results in more obvious protein oxidation in relation to oxidative stress. The increased expression of VEGF and TGF-ß(1) in the context of hypoxia is closely related to AOPP level.

[A study on the heterogeneous apoptosis of lymphocytes, eosinophils, and neutrophils from peripheral blood of asthmatic patients].

OBJECTIVES: To observe different responsiveness of lymphocytes, eosinophils, and neutrophils from peripheral blood of asthmatic patients to dexamethasone and montelukast-induced apoptosis and to explore the roles of Fas antigen and caspase-3 in the heterogeneity of cell apoptosis. METHODS: Lymphocytes, eosinophils, and neutrophils were isolated from peripheral blood of 18 asthmatic patients. Cells were incubated in vitro and treated with dexamethasone and leukotriene receptor antagonist montelukast respectively. Cell apoptosis rates and Fas expression rates were examined by flowcytometry whereas caspase-3 levels in these cells were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: (1) Apoptosis rates: in vitro lymphocytes, eosinophils and neutrophils were compromised of spontaneous apoptosis at lower rates [(6.9 +/- 0.7)%, (31 +/- 11)% and (32 +/- 30)%, respectively]. With induction of dexamethasone, the apoptosis rates were (17.1 +/- 10.8)%, (44 +/- 22)% and (35 +/- 24)%. Montelukast markedly elevated the apoptosis rates of these three cells [(22.5 +/- 17.6)%, (50 +/- 27)% and (55 +/- 22)%, respectively] (compared to control, P < 0.01, < 0.05, > 0.05, respectively). (2) Fas expression: lymphocytes, eosinophils and neutrophils expressed low levels of Fas antigen at baseline [(1.50 +/- 0.07)%, (2.20 +/- 0.10)% and (1.21 +/- 0.09)%, respectively]. Dexamethasone induced Fas antigen expression levels of these cells of (6.58 +/- 2.10)%, (7.52 +/- 3.20)% and (3.24 +/- 2.34)%, and montelukast induced the expression levels of (5.06 +/- 1.66, 7.45 +/- 2.63, 3.03 +/- 2.47, P < 0.01, < 0.01, > 0.05, respectively). (3) caspase-3 levels: lymphocytes, eosinophils and neutrophils expressed constitutive caspase-3 levels of [(3.3 +/- 2.9) ng/L, (5 +/- 4) ng/L and (4.3 +/- 2.6) ng/L, respectively]. The dexamethasone induced caspase-3 levels were (6.7 +/- 3.1) ng/L, (6 +/- 3) ng/L and (3.1 +/- 1.8) ng/L. The montelukast induced levels were (5.2 +/- 3.7) ng/L, (8 +/- 4) ng/L, and (3.1 +/- 2.0) ng/L (compared to control, P < 0.01, < 0.01, > 0.05, respectively). It was demonstrated that dexamethasone and montelukast significantly induced apoptosis of lymphocytes and eosinophils which were assocreased with increased expression of Fas antigen and caspase-3. Dexamethasone was incapable of inducing neutrophils to apoptosis and had no significant effects on Fas expression and caspase-3 activity. Neutrophils underwent significant apoptosis after montelukast treatment, however, the induction was unlikely to be regulated by Fas and caspase-3 pathway. CONCLUSIONS: In asthmatic inflammatory modulating and effective cells, neutrophils is distinct from lymphocytes and eosinophils in profile of apoptosis induced by glucocorticoids and leukotriene receptor antagonist. The signal pathway contributing neutrophil apoptosis heterogeneity may involve deficient caspase cascade or Fas/FasL.

[Effect of montelukast on the apoptosis of lymphocytes in asthmatic rats and its molecular mechanism].

OBJECTIVE: To investigate the effect of montelukast(MK) on the apoptosis of lymphocytes and the associated molecular mechanism in asthmatic rats in vivo and in vitro. METHODS: The asthmatic model was established by sensitizing and challenging SD rat with ovalbumin (OVA). Forty male SD rats were randomly divided into control group, asthma group, MK-treated group and Dexamethason (DXM)-treated group. T lymphocytes were labeled with CD(4)+ and CD(8)+ antibodies and then labeled with TdT-mediated dUTP nick end labeling (TUNEL) to detect apoptotic cells, and immunohistochemical staining of Fas antigen (CD95) was performed to detect Fas positive cells. The influences of MK on apoptosis and Fas antigen spontaneous expression on CD(4)+ / CD(8)+ lymphocytes in vivo and in vitro were assayed. RESULTS: The apoptosis rates of T lymphocytes from peripheral blood and lung tissue of asthmatic rats pre-treated by MK were significantly elevated as compared with those in normal control and asthma groups. In vitro culture MK was found to induce in dose- and time-dependent manner the apoptosis of peripheral blood lymphocytes pre-treated with OVA. A synergic effect of MK and DXM was demonstrated, i.e. MK in 10(-6) mol/L concentration markedly promoted the induction of apoptosis and expression of Fas antigen by 10(-6) mol/L DXM. CONCLUSION: MK could induce apoptosis of peripheral blood and lung lymphocytes (mainly CD(4)+) in asthmatic rats, which may be mediated by Fas system. The induction of apoptosis of lymphocytes by MK may contribute to anti-inflammation mechanisms. Furthermore, a synergic effect of MK and DXM on the induction of apoptosis of lymphocytes might exist.